OBJECTIVES: 1. 2'-Deoxyribonucleoside triphosphate analogs, especially analogs of dATP, will be synthesized by large-scale enzymic reduction of the corresponding ribonucleotides. The latter will be obtained by chemical phosphorylation of available nucleosides, especially tubercidin, formycin, toyocamycin and sangivamycin. For the enzymic reduction step ribonucleotide reductases of appropriate specificity from L. leichmannii, E. coli and other bacteria will be employed. 2. The effect of natural 2'-deoxyribonucleotides and the analogs prepared as above will be tested as inhibitors of ribonucleotide reductase from a himan lymphoblastic cell line. 3. 2'-Deoxyribonucleosides such as 2'-deoxytubercidin will be prepared by enzymatic dephosphorylation of the corresponding nucleotides obtained as above. The nucleoside analogs will be tested for cytotoxic action against human cells and L1210, a murine lymphoma, in culture and will be submitted to NCI for testing in the tumor screen. 4. (2'-3H)-2'-Deoxyribonucleosides and their 5'-triphosphates will be synthesized enzymatically and their metabolism investigated in human cells in culture.